This project involves the development and validation of radio-immunoassays for the measurement of "bone-specific" proteins in serum and urine. These will be used to assess bone formation and resorption in age-related bone loss and metabolic bone diseases. At first, the focus will be on bone Gla protein, osteonectin; then, on other noncollagenous bone-specific proteins, as these are isolated in Project 0003 and antibodies are developed. Assay of skeletal alkaline phosphatase which is near clinical usefulness will also be utilized in this project. A library of monoclonal and polyclonal antibodies to the proteins isolated on Project 0003 will be developed. Normal values will be established in healthy individuals of both sexes from ages 20-90 years. Criteria for exclusion of patients with bone disease are outlined. Studies will then be performed in patients with osteoporosis, hyperparathyroidism, hyperthyroidism, Paget's disease, steriod-induced osteoporosis, and other metabolic bone diseases, as well as patients with osteogenic sarcoma, and carcinoma of the prostate. The relationship to vitamin D metabolism will be evaluated by comparing serum levels in patients with vitamin D deficiency and subjects with hypervitaminosis D.